Humans exhibit a wide range of vulnerability to sound exposure. These individual differences make it difficult to develop accurate guidelines for hearing conservation that are effective and realistic for an industrialized society. The strength of natural olivocochlear (OC) efferent feedback mechanisms may be a primary determinant of individual susceptibility to noise-induced hearing loss accumulated over a lifetime. To test this hypothesis, Aim 1 will relate patterns of hearing loss to the OC function of laboratory mice. The strength of OC function will be manipulated by selecting subjects from normal strains based on physiological criteria, investigating inbred strains with compromised OC systems, and disrupting OC signaling in genetically engineered mice. There is strong evidence that OC neurons protect the ear from sound exposure. The ecological significance of the protective effect has been questioned because it has been demonstrated only at extreme sound levels. OC neurons may also protect the ear from the accrued effects of long-term moderate sound exposure. Aging subjects in quiet versus moderate sound levels will test this hypothesis. Cochlear integrity will be evaluated with distortion product otoacoustic emissions and auditory brainstem responses. The chronology of hearing loss will be characterized longitudinally within groups of mice that are defined by age, OC strength, and cumulative sound exposure. Based on human communication impairments, elevated physiological thresholds are expected to represent the endpoint of a functional decline that begins earlier as deficits in listening in noise. Aim 2 will confirm this prediction by tracking the perceptual changes in each group with a signal-in-noise behavioral task. The objective is to demonstrate behavioral deficits in background noise before the onset of physiological threshold shifts. The anatomical correlates of these diverse forms of hearing loss have been difficult to isolate because experimental animals, like humans, show large individual differences in the rate and pattern of impairment. The physiological and behavioral phenotypes achieved in the experiments of Aims 1 and 2 provide an ideal context for investigating the anatomical basis of hearing loss and concurrent compensatory mechanisms in the inner ear. Aim 3 will use quantitative immunofluorescence and electron microscopic analyses to describe the afferent and efferent synaptic complexes of mice with known processing deficits. Long-term maintenance of auditory function is predicted to require the survival of afferent neurons and functional efferent innervation. Relevance: Results from this work will lead to a better understanding of the protective effects of the OC system, and may lead to better hearing loss prevention strategies in humans. [unreadable] [unreadable] [unreadable] [unreadable]